Hemodialysis (HD) patients have reduced circulating levels of 1,25-OH vitamin D levels because its major site of production is the healthy kidney via the 1-alpha hydroxylase enzyme. The deficiency is treated with intravenous1,25-OH active vitamin D at dialysis which is titrated to achieve a targeted parathyroid hormone (PTH) value recommended by the National Kidney Foundation (NKF) Kidney Dialysis Outcomes Quality Initiative (KDOQI) Guidelines. Despite these intravenous vitamin D treatments, HD patients have a very high prevalence of 25-OH vitamin deficiency. 25-OH deficiency has been associated with poor neuromuscular function and cognition in non-dialysis populations. The role vitamin 25-OH D deficiency in the highly prevalent muscle weakness and cognitive impairment experienced by HD patients is currently not known. Since many tissues other than the kidney possess the 1-alpha hydroxylase enzyme capable of activating 25 OH vitamin D to 1-25 OH vitamin D, administering IV active vitamin D solely to target a PTH range may completely neglect important vitamin D on other extra-skeletal tissues. The primary goal of our study is to determine the effect of vitamin D supplementation on neuromuscular and cognitive function in HD patients with 25-OH vitamin D levels <20 ng/ml. We propose a prospective, randomized, [double-blind placebo controlled] trial. Enrolled participants will be randomized 2:1 to receive vitamin D (n=20) or [placebo] (n=10) for 6 months. Following baseline neuromuscular and cognitive assessments, the treatment group will receive 50,000 IU of oral ergocalciferol every two weeks for 6 months, and have 25(OH) vitamin D3 levels re-measured at monthly intervals. Following 6 months of vitamin D supplementation, neuromuscular and cognitive assessments will be performed. Results from neuromuscular function and cognitive assessments between the [placebo] arm and treatment will be analyzed as well as differences in assessments prior to and following the 6 month interval in both groups. PUBLIC HEALTH RELEVANCE: The outpatient HD unit at the James J. Peters VAMC has grown nearly 15% each year for the past two years and is one of the largest VA dialysis centers. Muscle weakness and cognitive impairment are common among HD patients and likely contributes to the high prevalence of falls in this population. Falls result in increased morbidity, decreased independence, and likely increases mortality. While cognitive impairment can contribute to falls it is also likely to result in poor compliance with complex medical treatments and medication regimens required of HD patients. Given the safety, low cost of supplementation, and potential clinical benefits of vitamin D treatment, we propose a study to evaluate its role in improving important clinical endpoints.